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Cutaneous microbiota features distinguish psoriasis from psoriatic arthritis [Meeting Abstract]

Manasson, J; Reddy, S M; Neimann, A L; Segal, L N; Scher, J U
Background/Purpose: Psoriasis (PsO) is a chronic immune-mediated skin condition affecting ~3% of adults worldwide. Up to a third of PsO patients go on to develop psoriatic arthritis (PsA), a heterogeneous inflammatory arthritis characterized by concomitant bone erosion and osteoproliferation. Although multiple advances have been made in the pathogenesis and therapeutics of these disorders, it is currently not possible to predict which individuals will progress from PsO to PsA. The role of the microbiome as a potential trigger for autoimmunity and rheumatic disease has recently been implicated. The goal of this study was to characterize the cutaneous microbiota of patients with PsO and PsA (in both psoriatic plaques and unaffected skin) to determine if there are characteristic features related to disease phenotype. Methods: Skin swabs from subjects with PsO (n=29) and PsA (n=62) were collected from both psoriatic plaque lesions and contralateral unaffected skin. 16S rDNA was extracted per protocol (MoBio, USA) and amplicons targeting the hypervariable V4 region were sequenced using MiSeq (Illumina) to define the microbiota composition. The obtained 16S rRNA sequences were analyzed using the Quantitative Insights into Microbial Ecology (QIIME) pipeline. Taxonomic relative abundance was determined to compare their prevalence among different phenotypes using Kruskal-Wallis statistical analysis. Alpha diversity plots and weighted Unifrac analysis (beta diversity) of cutaneous bacterial communities were generated. False discovery rate analysis was applied to identify unique differentiating taxa. Results: Baseline characteristics were comparable in both groups. PsO samples had, on average, a similar number of operational taxonomic units as compared to PsA samples. Beta diversity plots did not demonstrate statistically distinct clustering of microbial communities between PsO and PsA subjects, PsO and PsA nonlesional skin, or PsO and PsA lesional skin. Staphylococcus and Corynebacterium were the most abundant genera across all samples. However, several genera were statistically more abundant in PsO compared to PsA lesions, including unclassified Bradyrhizobiaceae (p<0.0006), Rahnella (p<0.0006), unclassified Prevotellaceae (p<0.001), and Parvibaculum (p<0.002). Rothia was more abundant in PsA (p<0.02). Conclusion: Our results characterize, for the first time, the cutaneous microbial composition of individuals with PsO compared to those with PsA both in psoriatic lesions and unaffected skin. Although we did not find overall community differences among the various phenotypes, our preliminary observations point towards differences in specific genera, which are characteristically more abundant in PsO. Further in-depth analysis is required to better understand the significance of this dysbiotic process in PsA and whether it contributes to the pathogenesis of the psoriatic disease spectrum. Current efforts are devoted to incorporating healthy controls into our analysis, and analyzing the cutaneous microbiome (and metagenome) across multiple body sites, multiple visits, as well as pre- and post-immunosuppressive/biologic therapy
EMBASE:613887986
ISSN: 2326-5205
CID: 2398062

IgA vasculitis (Henoch-Schonlein purpura)

Farhadian, Joshua A; Castilla, Carmen; Shvartsbeyn, Marianna; Meehan, Shane A; Neimann, Andrea; Pomeranz, Miriam Keltz
We report the first case of direct immunoflourescence-proven immunoglobulin A (IgA) vasculitis associated with influenza infection in an adult patient. IgA vasculitis, which was previously known as Henoch-Schonlein purpura, is the most common systemic vasculitis in children but rarely occurs in adults. Disease onset often occurs after upper respiratory tract infections that are caused by adenovirus or enterovirus. The American College of Rheumatology defines IgA vasculitis by the presence of any two of the following four criteria: age
PMID: 26990342
ISSN: 1087-2108
CID: 2051352

Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme disease

Mazori, Daniel R; Orme, Charisse M; Mir, Adnan; Meehan, Shane A; Neimann, Andrea L
Erythema migrans is the initial sign in the majority of patients infected with Borrelia, the genus of spirochetes that causes Lyme disease. Early identification and treatment decrease the risk of progression to later stages of disease. Although a "bull's eye" appearance owing to lesional clearing is considered classic for erythema migrans, this feature is surprisingly often lacking among patients in the United States. Furthermore, cutaneous Lyme disease can exhibit a wide range of morphologic variability in a minority of patients. Herein, we describe the case of a patient with Lyme disease in which the presence of atypical vesicular features, in conjunction with the initial absence of clearing, resulted in multiple misdiagnoses and delayed treatment. We also review the literature on the epidemiology and management of erythema migrans for cases in which the diagnosis may pose a challenge.
PMID: 26437159
ISSN: 1087-2108
CID: 1793082

Reply [Letter]

Scher, Jose U; Reddy, Soumya; Ubeda, Carles; Neimann, Andrea; Abramson, Steven B
PMCID:4519415
PMID: 25891517
ISSN: 2326-5205
CID: 1697942

Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease

Scher, Jose U; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G; Littman, Dan R; Abramson, Steven B
OBJECTIVE: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). METHODS: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. RESULTS: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. CONCLUSION: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.
PMCID:4280348
PMID: 25319745
ISSN: 2326-5205
CID: 1453542

Cause-specific mortality in patients with severe psoriasis: A population-based cohort study [Meeting Abstract]

Abuabara, Katrina; Neimann, Andrea; Troxel, Andrea; Shin, Daniel; Azfar, Rahat
ISI:000286780500028
ISSN: 0190-9622
CID: 2230812

Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K

Abuabara, K; Azfar, R S; Shin, D B; Neimann, A L; Troxel, A B; Gelfand, J M
BACKGROUND: Severe psoriasis is associated with excess mortality and increased risk of cardiovascular death. Population-based data evaluating cause-specific mortality in patients with psoriasis are limited. OBJECTIVES: To describe cause-specific mortality in patients with severe psoriasis. METHODS: We performed a cohort study from 1987 to 2002 of patients >/=18 years using the General Practice Research Database. We compared patients with a psoriasis code and a history of systemic therapy consistent with severe psoriasis (n=3603) with patients with no history of psoriasis (n=14,330). Age- and sex-adjusted Cox models were created for each of the leading causes of death defined by the Centers for Disease Control. RESULTS: Patients with severe psoriasis were at increased risk of death from cardiovascular disease [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.26-1.96], malignancies (HR 1.41, 95% CI 1.07-1.86), chronic lower respiratory disease (HR 2.08, 95% CI 1.24-3.48), diabetes (HR 2.86, 95% CI 1.08-7.59), dementia (HR 3.64, 95% CI 1.36-9.72), infection (HR 1.65, 95% CI 1.26-2.18), kidney disease (HR 4.37, 95% CI 2.24-8.53) and unknown/missing causes (HR 1.43, 95% CI 1.09-1.89). The absolute and excess risk of death was highest for cardiovascular disease (61.9 and 3.5 deaths per 1000 patient-years, respectively). CONCLUSIONS: Severe psoriasis is associated with an increased risk of death from a variety of causes, with cardiovascular death being the most common aetiology. These patients were also at increased risk of death from causes not previously reported, such as infection, kidney disease and dementia. Additional studies are necessary to determine the degree to which excess causes of death are due to psoriasis, its treatments, associated behaviours, or other factors
PMCID:2966545
PMID: 20633008
ISSN: 1365-2133
CID: 135072

Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database

Mehta, Nehal N; Azfar, Rahat S; Shin, Daniel B; Neimann, Andrea L; Troxel, Andrea B; Gelfand, Joel M
AIMS: Psoriasis is a common chronic inflammatory T-helper cell-1/17 mediated skin disease. Recent studies suggest that psoriasis, particularly if severe, may be an independent risk factor for atherosclerosis, myocardial infarction (MI), and stroke. We conducted a cohort study using the General Practice Research Database to determine if severe psoriasis patients have an increased risk of cardiovascular (CV) mortality. METHODS AND RESULTS: Severe psoriasis was defined as patients who received a psoriasis diagnosis and systemic therapy consistent with severe psoriasis (n = 3603). Up to four unexposed patients without psoriasis were selected from the same practices and start dates for each psoriasis patient (n = 14 330). For every death, the cause was determined by review of the electronic medical record. Severe psoriasis was an independent risk factor for CV mortality (HR 1.57; 95% CI 1.26, 1.96) when adjusting for age, sex, smoking, diabetes, hypertension, and hyperlipidaemia. Overall, severe psoriasis patients experienced one extra CV death per 283 patients per year, even when adjusting for major CV risk factors. The relative risk of CV mortality was modified by age. For example, the RR of CV death for a 40-year-old and 60-year-old with severe psoriasis was 2.69 (1.45, 4.99) and 1.92 (1.41, 2.62), respectively. The findings were robust to multiple sensitivity analyses. CONCLUSION: Patients with severe psoriasis have an increased risk of CV mortality that is independent of traditional CV risk factors. Additional studies are needed to determine the mechanism of this association and the impact that control of psoriasis has on CV risk
PMCID:2894736
PMID: 20037179
ISSN: 1522-9645
CID: 135066

Patients With Severe Psoriasis and No History of Cardiovascular Disease Are at Increased Risk of Cardiovascular Mortality [Meeting Abstract]

Mehta, Nehal N; Azfar, Rahat S; Shin, Daniel B; Neimann, Andrea L; Troxel, Andrea B; Gelfand, Joel M
ISI:000271831501159
ISSN: 0009-7322
CID: 2230802

Psoriasis and risk of myocardial infarction - Reply [Letter]

Gelfand, Joel M; Kurd, Shanu Kohli; Neimann, Andrea L; Shin, Daniel B; Troxel, Andrea B
ISI:000243645400020
ISSN: 0098-7484
CID: 2230712